Insulin receptors and responsiveness have been studied in undifferentiated and fatty 3T3-L1fibroblasts. Glucocorticoid hormones induce insulin resistance in 3T3-L1 cells. The affinity of the receptor for insulin is decreased and there is inhibition of the insulin response at a post-receptor site. Membrane lipids can be modified by growth of cells in media containing different saturated and unsaturated fatty acids. Saturated fatty acids result in a decrease in both insulin binding and action.